As of early September 2021, the COVID-19 pandemic caused by the SARS-CoV-2 virus has affected over 200 million people and led to 4.4 million deaths worldwide. In India alone, 3,30,00,000 COVID-19 cases and 4,42,000 COVID-19 related deaths have been reported to date. While most infections are mild with respiratory symptoms, a severe form of the disease is seen in older adults and people with chronic heart, kidney and lung diseases, diabetes or other conditions that render the immune system weak. COVID-19 damages many organs including the lungs, heart and kidneys.
Kidney injury as a complication of COVID-19 is more commonly seen in hospitalised patients. While the reported prevalence of kidney injury was 7% in a study of 2,650 patients admitted to a large hospital in southern India, a recent large study in the United States reported kidney injury in as many as 46% of 3,993 hospitalised patients, of whom 19% required dialysis. Patients with COVID-19 kidney injury also have increased duration of hospitalisation, with increased health-care costs. Unfortunately, there are many more deaths in those who have acute kidney injury.
Understanding the microscopic changes in kidneys after infection with the SARS-CoV-2 virus is important and has been the focus of extensive research. Researchers, especially pathologists, across the globe have been unified in their observations of COVID-19 kidney injury — i.e., acute tubular injury (injury of the transporting channels in the kidney) is the hallmark of kidney pathology. Thrombi or blood clots, as seen in the lungs and heart, may also be seen in the kidney. Inflammation (influx of white blood cells) in the kidney has also been described by researchers. The kidney injury is more commonly seen in kidneys that already have chronic injury, such as that seen in diabetes or severe blood vessel diseases.
The exact process in which the SARS-CoV-2 virus brings on the kidney injury has been studied to varying detail by different centres. The first question asked is: does the virus directly damage the kidney? Many centres across the globe have used a very special microscope called the electron microscope to look for evidence of virus in the kidney. The initial studies that emerged from China and the United States seemed to identify structures within kidney cells that looked like viral particles. This seemed to be logical, given that the kidney has a high concentration of ACE2, which is the key protein structure on a cell that the SARS-CoV-2 virus attaches to. This step is critical for the virus to enter the cell. However, as more research was done, it became clear that what was once thought to be viral particles in cells were, in fact, increased numbers of vesicles (structures in the cell that are used in sending important signals) and were mere viral mimics. Even specific staining techniques to detect very small amounts of viral proteins failed to show virus in the kidneys. All of this suggested that direct viral injury was not the main method of kidney injury. If not, then how was the SARS-CoV-2 virus injuring the kidney?
The main focus of our own research was to understand how SARS-CoV-2 causes kidney injury and how the proteins and genes change in kidneys after COVID-19 infection. This study from in , points to a strong immune response (immune response is the way the body fights against substances it sees as foreign or harmful) in the kidneys. The immune response was seen in all parts of the kidney tissue, including the small blood vessels and in the glomerulus (filtering unit of the kidney). This was mostly seen in those with severe cases of COVID-19. We were able to show two pathways of immune response to the kidneys; Innate immunity, which is the non-specific response you are born with, to fight harmful organisms. In COVID-19 kidneys, we found a rich infiltrate of white blood cells (called macrophages) in the kidneys. Adaptive immune response, which is the body’s acquired immune response to the SARS-CoV-2 virus, was evident by an increase in specific type of immune (T cells) in the kidney tissue. This was shown using state-of-the-art techniques, including transcriptomic, proteomics and mass-cytometry. Mayo Clinic, recently publishedThe Mayo Clinic Proceedings
Several experts in the field had been suggesting that the kidney injury in severe COVID-19 behaves similar to kidney injury from sepsis, which is the body’s extreme response to an infection. In our study, we were able to compare the findings in COVID-19 kidney injury with kidneys from individuals with known sepsis, and indeed, found that the immune response in the two were very similar. This finding perhaps emphasises the need to manage COVID-19 patients in the same way as patients with sepsis. The observations from our tissue proteins analysis and ultrastructural analysis points also to mitochondria, (which is the powerhouse of the cell) bearing the final insult of the SARS-CoV-2. While this finding is unique to COVID-19 kidney injury, it lends important insight into potential treatment strategies that could be used in managing COVID-19.
In conclusion, this Mayo Clinic study is important in that it emphasises a few important facts. First, there is a great need for researchers to capitalise on the patient specimens collected during the pandemic and gather and store data for current and future use. Data archived for future studies will potentially provide valuable information in the event of another pandemic. Second, it will allow the study of COVID-19 associated tissue injury in different populations. Third, by using state-of-the-art technology tools, we were able to analyse the body’s immune response to the virus, and how this response might be injuring kidneys. Taken together, the severe kidney injury seen in COVID-19 further supports the need for widespread vaccination to protect everyone from this viral infection.
Dr. Mariam Priya Alexander is Associate Professor of Pathology, Mayo Clinic, Rochester, Minnesota, U.S.
Dr. Timucin Taner is Associate Professor, Transplant Surgeon and Immunologist, Mayo Clinic, Rochester, Minnesota, U.S.
